Inhlanganisela yokuqala ye-LAG-3-Blocking antibody, i-Opdualag™ (i-nivolumab ne-relatlimab-rmbw), igunyazwe yi-FDA ezigulini ezinemelanoma engahlanjululwayo noma ye-metastatic.

April 2022: I-US Food and Drug Administration (FDA) igunyaze I-Opdualag (nivolumab ne-relatlimab-rmbw), inhlanganisela yomthamo ongaguquki omusha, wesigaba sokuqala se-nivolumab kanye ne-relatlimab elawulwa njengokufakwa emthanjeni okukodwa, ukuze kwelashwe iziguli zabantu abadala kanye nezingane ezineminyaka engu-12 ubudala nangaphezulu ezinemelanoma enganqamuki noma ye-metastatic. Ukugunyaza kususelwe ocwaningweni lwe-RELATIVITY-047 Isigaba 2/3, oluqhathanise i-Opdualag (n=355) ne-nivolumab iyodwa (n=359) kusibalo sabantu abangu-355.

The trial met its primary endpoint, progression-free survival (PFS), and I-Opdualag ngaphezu kokuphindwe kabili i-PFS emaphakathi uma iqhathaniswa ne-nivolumab i-monotherapy, izinyanga ze-10.1 (I-95% Isikhathi Sokuqiniseka [CI]: 6.4 kuya ku-15.7) ngokumelene nezinyanga ze-4.6 (95% CI: 3.4 kuya ku-5.6); (I-Hazard Ratio [HR] 0.75; 95% CI: 0.62 kuya ku-0.92, P= 0.0055).¹ The I-Opdualag iphrofayili yokuphepha yayifana naleyo ebibikwe ngaphambilini nge-nivolumab.^1,2 Ayikho imicimbi emisha yokuphepha ekhonjwe ngenhlanganisela uma iqhathaniswa ne-nivolumab monotherapy.^1,2 Izehlakalo ezingezinhle eziphathelene nezidakamizwa zeBanga lesi-3/4 bezingu-18.9%. I-Opdualag ingalo uma iqhathaniswa ne-9.7% engalweni ye-nivolumab.² Izehlakalo ezimbi ezihlobene nezidakamizwa eziholele ekuyekisweni bekungama-14.6% ku- I-Opdualag ingalo uma iqhathaniswa ne-6.7% engalweni ye-nivolumab.²

“Since the approval of the first immune checkpoint inhibitor more than 10 years ago, we’ve seen immunotherapy, alone and in combination, revolutionize the treatment of patients with advanced melanoma,” said F. Stephen Hodi, M.D., director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber Cancer Institute.³ “Ukugunyazwa kwanamuhla kubaluleke kakhulu, njengoba kunjalo introduces an entirely new combination of two immunotherapies that may act together to help improve anti-tumor response by targeting two different immune checkpoints — LAG-3 and PD-1.”^1,2

I-Opdualag is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions (IMARs) including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, myocarditis and other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); and embryo-fetal toxicity.¹ Sicela ubheke Ulwazi Olubalulekile Lokuphepha ngezansi.

“While we have made great progress in the treatment of advanced melanoma over the past decade, we are committed to expanding dual immunotherapy treatment options for these patients,” said Samit Hirawat, chief medical officer, global drug development, Bristol Myers Squibb.³ “Ukuvimbela i-LAG-3 nge-relatlimab, ekuhlanganisweni komthamo ongaguquki ne-nivolumab, kumelela indlela entsha yokwelapha eyakhela phezu kwefa lethu lokuletha izinketho ezintsha zokwelashwa kwe-immunotherapy ezigulini. Ukugunyazwa komuthi omusha ohlanganisa i-checkpoint inhibitor yethu yesithathu ehlukile kuphawula igxathu elibalulekile eliya phambili ekunikezeni iziguli izinketho ezengeziwe ngaphandle kokwelashwa okukodwa.”

I-Lymphocyte activation gene-3 (LAG-3) kanye ne-programmed death-1 (PD-1) yizindawo ezimbili ezihlukene zokuhlola amasosha omzimba avame ukuvezwa ngokuhlanganyela kuma-lymphocyte angena ngesimila, ngaleyo ndlela abe nomthelela ekukhathaleni kwe-T-cell okune-tumor.² Inhlanganisela ye-nivolumab (i-anti-PD-1) kanye ne-relatlimab (i-anti-LAG-3) iphumela ekwandeni kokusebenza kwe-T-cell uma kuqhathaniswa nomsebenzi wanoma iyiphi i-antibody yodwa.¹ I-Relatlimab (ihlanganiswe ne-nivolumab) iyi-antibody yokuqala evimba i-LAG-3 ukubonisa inzuzo ocwaningweni lweSigaba sesi-3.¹ Kuyi-inhibitor yesithathu yokuhlola (kanye ne-anti-PD-1 ne-anti-CTLA-4) ye-Bristol Myers Squibb.

“Ukugunyazwa kwanamuhla kuyizindaba ezijabulisayo futhi kunikeza ithemba elisha emphakathini we-melanoma. Ukutholakala kwale nhlanganisela yokwelashwa kungase kwenze iziguli zikwazi ukuzuza ekwelashweni okubili kokuzivikela komzimba okusha, kokuqala kwekilasi lokuqala,” kusho uMichael Kaplan, umongameli kanye ne-CEO, iMelanoma Research Alliance.

Umthamo ogunyazwe yi-FDA weziguli zabantu abadala kanye neziguli zezingane ezineminyaka engu-12 ubudala noma ngaphezulu ezinesisindo esingenani esingama-40 kg ngu-480 mg nivolumab kanye ne-160 mg relatlimab esetshenziswa ngomthambo njalo emavikini amane.¹ Umthamo onconyiwe weziguli zezingane ezineminyaka engu-12 ubudala noma ngaphezulu ezinesisindo esingaphansi kwama-40 kg, kanye neziguli zezingane ezingaphansi kweminyaka engu-12 ubudala, awukaziwa.¹

Lolu hlelo lokusebenza lugunyazwe ngaphansi kohlelo lokuhlola lwe-FDA lwe-Real-Time Oncology Review (RTOR), oluhlose ukuqinisekisa ukuthi ukwelapha okuphephile nokusebenzayo kuyatholakala ezigulini ngokushesha okukhulu.⁴ Ukubuyekezwa kuphinde kwenziwa ngaphansi kohlelo lwe-FDA's Project Orbis, oluvumele ukubuyekezwa ngasikhathi sinye yiziphathimandla zezempilo e-Australia, Brazil naseSwitzerland, lapho isicelo sisabuyekezwa.

Mayelana ne-RELATIVITY-047

I-RELATIVITY-047 iwucwaningo lomhlaba wonke, olungahleliwe, olungaboni kabili lweSigaba 2/3 oluhlola inhlanganisela yomthamo ongaguquki we-nivolumab kanye ne-relatlimab iqhathaniswa ne-nivolumab iyodwa ezigulini ezinemelanoma ye-metastatic engazange iphathwe noma engahosheki.^1,2 Ukuhlolwa bekungabandakanyi iziguli ezinesifo esisebenzayo sokuzivikela komzimba, izimo zezokwelapha ezidinga ukwelashwa okuhlelekile nge-corticosteroids yomthamo omaphakathi noma ophezulu noma imithi ye-immunosuppressive, i-uveal melanoma, nobuchopho obusebenzayo noma obungelashiwe noma i-leptomeningeal metastases.¹ Isiphetho esiyinhloko socwaningo ukusinda kwe-progression-free (PFS) okunqunywe yi-Blinded Independent Central Review (BICR) kusetshenziswa Izimo Zokuhlola Izimpendulo Kumathumba Aqinile (RECIST v1.1).¹ Iziphetho zesibili ukusinda sekukonke (OS) kanye nezinga lokuphendula lenhloso (ORR).¹ Isamba seziguli ze-714 zahlelwa ngokungahleliwe ku-1: 1 ukuze zithole inhlanganisela yomthamo ongaguquki we-nivolumab (480 mg) ne-relatlimab (160 mg) noma i-nivolumab (480 mg) ngokufakwa komthambo njalo emavikini amane kuze kube yilapho isifo siqhubeka noma ubuthi obungamukeleki.¹

Khetha Iphrofayela Yokuphepha Kusuka ku-RELATIVITY-047

Ukusabela okubi okuholela ekuyekisweni unomphela kwe I-Opdualag kwenzeka ku-18% weziguli.¹I-Opdualag yaphazamiseka ngenxa yokusabela okungekuhle kuma-43% eziguli.¹ Ukusabela okubi kakhulu kwenzeka kuma-36% eziguli ezelashwe ngazo I-Opdualag.¹ Okuvame kakhulu (≥1%) ukusabela okubi kakhulu kwaba ukungasebenzi kahle kwezindlala ze-adrenal (1.4%), i-anemia (1.4%), i-colitis (1.4%), inyumoniya (1.4%), i-acute myocardial infarction (1.1%), ubuhlungu beqolo (1.1%) ), isifo sohudo (1.1%), i-myocarditis (1.1%), kanye ne-pneumonia (1.1%).¹ Ukusabela okubi okuyingozi kwenzeka ezigulini ezintathu (0.8%) ezelashwe ngazo I-Opdualag futhi yayihlanganisa i-hemophagocytic lymphohistiocytosis, i-acute edema yamaphaphu, kanye ne-pneumonia.¹ Okuvame kakhulu (≥20%) ukusabela okubi kwakuwubuhlungu be-musculoskeletal (45%), ukukhathala (39%), ukuqubuka (28%), pruritus (25%), nesifo sohudo (24%).¹ The I-Opdualag iphrofayili yokuphepha yayifana naleyo ebibikwe ngaphambilini nge-nivolumab.^1,2 Ayikho imicimbi emisha yokuphepha ekhonjwe ngenhlanganisela uma iqhathaniswa ne-nivolumab monotherapy.^1,2 Izehlakalo ezingezinhle eziphathelene nezidakamizwa zeBanga lesi-3/4 bezingu-18.9%. I-Opdualag ingalo uma iqhathaniswa ne-9.7% engalweni ye-nivolumab.² Izehlakalo ezimbi ezihlobene nezidakamizwa eziholele ekuyekisweni bekungama-14.6% ku- I-Opdualag ingalo uma iqhathaniswa ne-6.7% engalweni ye-nivolumab.²

Mayelana ne-Melanoma

I-melanoma iwuhlobo lomdlavuza wesikhumba obonakala ngokukhula okungalawuleki kwamangqamuzana akhiqiza umbala (ama-melanocyte) atholakala esikhumbeni.⁵ I-Metastatic melanoma iwuhlobo olubulalayo kakhulu lwesifo futhi yenzeka lapho umdlavuza usakazeka ngale kwesikhumba uye kwezinye izitho.^5,6 Izibalo ze-melanoma ziye zanda kancane kancane kule minyaka engu-30 edlule.^5,6 E-United States, cishe izifo ezintsha ezingama-99,780 ze-melanoma kanye nokufa okuhlobene cishe nezi-7,650 kulinganiselwa ku-2022.⁵ I-melanoma ingalapheka kakhulu uma ibanjwe isesigabeni sayo sokuqala; nokho, amazinga okusinda angancipha njengoba isifo siqhubeka.⁶

OPDUALAG INkomba

I-Opdualag ^TM (i-nivolumab ne-relatlimab-rmbw) iboniswa ekwelapheni iziguli ezindala kanye nezingane ezineminyaka engu-12 ubudala noma ngaphezulu ezine-melanoma engabonakali noma e-metastatic.

OPDUALAG ULWAZI OLUBALULEKILE LOKUPHEPHA

Ukusabela Okubi Okunamandla Futhi Okubulalayo Komzimba

Ukusabela okungekuhle kwe-immune-mediated adverse (IMAR) okubalwe lapha kungase kungafaki konke ukusabela okunamandla nokubulalayo okubangelwa amasosha omzimba.

Ama-IMAR angase abe nzima noma abulale, angenzeka kunoma yiluphi uhlelo lwesitho noma izicubu. Ama-IMAR angenzeka noma kunini ngemva kokuqala ukwelashwa nge-LAG-3 kanye ne-PD-1/PD-L1 evimbela amasosha omzimba. Ngenkathi ama-IMAR evamise ukubonakala phakathi nokwelashwa, angase futhi enzeka ngemva kokuyekiswa kwe-Opdualag. Ukuhlonzwa kusenesikhathi nokuphathwa kwama-IMAR kubalulekile ukuze kuqinisekiswe ukusetshenziswa okuphephile. Gada iziguli eduze ukuze uthole izimpawu nezimpawu ezingase zibe ukubonakaliswa komtholampilo kwama-IMAR angaphansi. Hlola amakhemikhali emitholampilo afaka ama-enzyme esibindi, i-creatinine, nomsebenzi we-thyroid ekuqaleni nangezikhathi ezithile phakathi nokwelashwa. Ezimeni zama-IMAR asolwayo, qala ukusebenza okufanele ukuze ukhiphe ezinye izimbangela, okuhlanganisa ukutheleleka. Faka ukuphathwa kwezokwelapha ngokushesha, okuhlanganisa ukubonisana okukhethekile njengoba kufanele.

Bamba noma yekisa unomphela i-Opdualag kuye ngobunzima (sicela ubheke isigaba 2 Umthamo Nokuphatha Olwazini Olugcwele Lokuchaza Okugcwele oluhambisana nalesi). Ngokuvamile, uma i-Opdualag idinga ukuphazanyiswa noma ukuyekiswa, nikeza ukwelashwa kwe-corticosteroid okuhleliwe (1 kuya ku-2 mg/kg/i-prednisone yosuku noma okulinganayo) kuze kube yilapho ithuthukiswa ku-Grade 1 noma ngaphansi. Lapho uthuthukela kuBanga loku-1 noma ngaphansi, qalisa i-corticosteroid taper futhi uqhubeke nokuthinta okungenani inyanga engu-1. Cabangela ukuphathwa kwamanye ama-systemic immunosuppressants ezigulini ama-IMAR azo angalawulwa ngokwelashwa kwe-corticosteroid. Imihlahlandlela yokulawulwa kobuthi yokusabela okubi okungadingi i-systemic steroids (isb, i-endocrinopathies kanye nokusabela kwesikhumba) kuxoxwa ngayo ngezansi.

I-Pneumonitis Yokuzivikela Emzimbeni

I-Opdualag ingabangela i-immune-mediated pneumonitis, engase ibulale. Ezigulini ezilashwa ngamanye amasosha omzimba avimba i-PD-1/PD-L1, izehlakalo ze-pneumonia ziphezulu ezigulini ezithole imisebe ye-thoracic ngaphambili. I-pneumonitis ye-immune-mediated pneumonia yenzeke ku-3.7% (13/355) yeziguli ezithola i-Opdualag, okuhlanganisa neBanga lesi-3 (0.6%), kanye neBanga lesi-2 (2.3%) ukusabela okungalungile. I-Pneumonitis iholele ekuyekisweni unomphela kwe-Opdualag ku-0.8% kanye nokubanjwa kwe-Opdualag ku-1.4% weziguli.

I-Immune-Mediated Colitis

I-Opdualag ingabangela i-immune-mediated colitis, echazwa ngokuthi idinga ukusetshenziswa kwe-corticosteroids futhi ayikho enye i-etiology ecacile. Uphawu oluvamile olufakwe encazelweni ye-colitis kwakuwuhudo. Ukutheleleka kwe-Cytomegalovirus / ukuvuselelwa kuye kwabikwa ezigulini ezine-corticosteroid-refractory immune-mediated colitis. Ezimweni ze-corticosteroid-refractory colitis, cabanga ukuphindaphinda ukusebenza okuthelelanayo ukuze ukhiphe ezinye izimbangela.

Uhudo olubangelwa amasosha omzimba noma i-colitis lwenzeka ku-7% (24/355) weziguli ezithola i-Opdualag, okuhlanganisa neBanga lesi-3 (1.1%) kanye neBanga lesi-2 (4.5%) ukusabela okungekuhle. I-Colitis iholele ekuyekisweni unomphela kwe-Opdualag ku-2% nokubanjwa kwe-Opdualag ku-2.8% weziguli.

I-Hepatitis Eyamasosha omzimba

I-Opdualag ingabangela isifo sokusha kwesibindi kokuzivikela komzimba, esichazwa ngokuthi sidinga ukusetshenziswa kwe-corticosteroids futhi ayikho enye indlela ecacile yokuvela kwayo.

Isifo sokusha kwesibindi kokuzivikela komzimba senzeka ku-6% (20/355) weziguli ezithola i-Opdualag, okuhlanganisa neBanga lesi-4 (0.6%), iBanga lesi-3 (3.4%), kanye neBanga lesi-2 (1.4%) ukusabela okungekuhle. I-Hepatitis iholele ekuyekisweni unomphela kwe-Opdualag ku-1.7% kanye nokubanjwa kwe-Opdualag ku-2.3% weziguli.

Ama-Endocrinopathies Azivikela Omzimba

Opdualag can cause primary or secondary adrenal insufficiency, hypophysitis, thyroid disorders, and Type 1 diabetes mellitus, which can be present with diabetic ketoacidosis. Withhold or permanently discontinue Opdualag depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

Ebangeni lesi-2 noma ngaphezulu kokungasebenzi kahle kwezindlala ze-adrenal, qala ukwelashwa okunezimpawu, okuhlanganisa nokushintshwa kwamahomoni njengoba kukhonjisiwe emtholampilo. Ezigulini ezithola i-Opdualag, ukungasebenzi kahle kwezindlala ze-adrenal kwenzeka ku-4.2% (15/355) weziguli ezithola i-Opdualag, okuhlanganisa ukusabela okungekuhle kweBanga lesi-3 (1.4%) kanye neBanga lesi-2 (2.5%). Ukungasebenzi kahle kwe-Adrenal kuholele ekuyekisweni unomphela kwe-Opdualag ku-1.1% kanye nokubanjwa kwe-Opdualag ku-0.8% weziguli.

I-Hypophysitis ingaba nezimpawu ezibucayi ezihambisana nomphumela omkhulu njengekhanda elibuhlungu, i-photophobia, noma ukukhubazeka okubonakalayo. I-Hypophysitis ingabangela i-hypopituitarism; qala ukushintshwa kwama-hormone njengoba kubonisiwe emtholampilo. I-Hypophysitis yenzeke ku-2.5% (9/355) weziguli ezithola i-Opdualag, okuhlanganisa neBanga lesi-3 (0.3%) kanye neBanga lesi-2 (1.4%) ukusabela okungekuhle. I-Hypophysitis iholele ekuyekisweni unomphela kwe-Opdualag ku-0.3% kanye nokubanjwa kwe-Opdualag ku-0.6% weziguli.

I-thyroiditis ingavela noma ngaphandle kwe-endocrinopathy. I-Hypothyroidism ingalandela i-hyperthyroidism; qala ukushintshwa kwama-hormone noma ukuphathwa kwezokwelapha njengoba kubonisiwe ngokomtholampilo. I-Thyroiditis yenzeke ku-2.8% (10/355) yeziguli ezithola i-Opdualag, okuhlanganisa ukusabela okungalungile kweBanga lesi-2 (1.1%). I-Thyroiditis ayizange iholele ekuyekisweni unomphela kwe-Opdualag. I-thyroiditis iholele ekubambeni kwe-Opdualag ku-0.3% weziguli. I-Hyperthyroidism yenzeke ku-6% (22/355) yeziguli ezithola i-Opdualag, kuhlanganise neBanga lesi-2 (1.4%) ukusabela okungalungile. I-Hyperthyroidism ayizange iholele ekuyekisweni unomphela kwe-Opdualag. I-Hyperthyroidism iholele ekubambeni kwe-Opdualag ku-0.3% yeziguli. I-Hypothyroidism yenzeke ku-17% (59/355) weziguli ezithola i-Opdualag, okuhlanganisa ukusabela okungalungile kweBanga lesi-2 (11%). I-Hypothyroidism iholele ekuyekisweni unomphela kwe-Opdualag ku-0.3% kanye nokubanjwa kwe-Opdualag ku-2.5% weziguli.

Gada iziguli nge-hyperglycemia noma ezinye izimpawu nezimpawu zesifo sikashukela; qala ukwelashwa nge-insulin njengoba kubonisiwe ngokomtholampilo. Isifo sikashukela senzeke ku-0.3% (1/355) weziguli ezithola i-Opdualag, ukusabela okungekuhle kweBanga lesi-3 (0.3%), futhi azikho izimo ze-ketoacidosis yesifo sikashukela. Isifo sikashukela asizange siholele ekuyekisweni unomphela noma ukubanjwa kwe-Opdualag kunoma yisiphi isiguli.

I-Nephritis Yokuzivikela Emzimbeni enokungasebenzi kahle kwe-Renal

I-Opdualag ingabangela i-immune-mediated nephritis, echazwa ngokuthi idinga ukusetshenziswa kwe-steroids futhi ayikho i-etiology ecacile. Ezigulini ezithola i-Opdualag, i-immune-mediated nephritis kanye nokungasebenzi kahle kwezinso kwenzeka ku-2% (7/355) weziguli, okuhlanganisa iBanga lesi-3 (1.1%) kanye neBanga lesi-2 (0.8%) ukusabela okungekuhle. I-nephritis evikela amasosha omzimba kanye nokungasebenzi kahle kwezinso kuholele ekuyekisweni unomphela kwe-Opdualag ku-0.8% kanye nokubanjwa kwe-Opdualag ku-0.6% weziguli.

Bamba noma yekisa unomphela i-Opdualag kuye ngobunzima (sicela ubheke isigaba 2 Umthamo Nokuphatha Olwazini Olugcwele Lokuchaza Okugcwele oluhambisana nalesi).

Ukusabela Okungahambi kahle Kwe-Dermatologic

I-Opdualag ingabangela ukuqubuka kwe-immune-mediated noma i-dermatitis, echazwe njengokudinga ukusetshenziswa kwe-steroids futhi ayikho enye i-etiology ecacile. I-exfoliative dermatitis, okuhlanganisa i-Stevens-Johnson syndrome, i-toxic epidermal necrolysis, kanye ne-Drug Rash ene-eosinophilia kanye nezimpawu zesistimu yenzekile nge-PD-1/L-1 evimbela amasosha omzimba. Ama-topical emollients kanye/noma ama-topical corticosteroids angase anele ukwelapha ukuqubuka okuthambile kuya kokumaphakathi okungakhiqizi.

Bamba noma yekisa unomphela i-Opdualag kuye ngobunzima (sicela ubheke isigaba 2 Umthamo Nokuphatha Olwazini Olugcwele Lokuchaza Okugcwele oluhambisana nalesi).

Ukuqubuka kwamasosha omzimba kwenzeka ku-9% (33/355) weziguli, okuhlanganisa iBanga lesi-3 (0.6%) kanye neBanga lesi-2 (3.4%) ukusabela okungekuhle. Ukuqubuka kwe-immune-mediated akuzange kuholele ekuyekisweni unomphela kwe-Opdualag. Ukuqubuka kwezivikeli mzimba kuholele ekubanjweni kwe-Opdualag ku-1.4% weziguli.

I-Myocarditis Ye-Immune-Mediated

I-Opdualag ingabangela i-myocarditis ye-immune-mediated, echazwa ngokuthi idinga ukusetshenziswa kwe-steroids futhi ayikho enye i-etiology ecacile. Ukuxilongwa kwe-myocarditis ye-immune-mediated kudinga inkomba ephezulu yokusola. Iziguli ezinezimpawu zenhliziyo noma ze-cardio-pulmonary kufanele zihlolwe ukuthi azikho yini i-myocarditis engaba khona. Uma kusolwa i-myocarditis, ugodle umthamo, ngokushesha qalisa umthamo omkhulu we-steroids (i-prednisone noma i-methylprednisolone 1 kuya ku-2 mg/kg/ngosuku) futhi uhlele ngokushesha ukubonisana kwenhliziyo nge-diagnostic workup. Uma kuqinisekisiwe ngokomtholampilo, yeka unomphela i-Opdualag yeBanga lesi-2-4 le-myocarditis.

I-Myocarditis yenzeke ku-1.7% (6/355) yeziguli ezithola i-Opdualag, okuhlanganisa iBanga lesi-3 (0.6%), kanye neBanga lesi-2 (1.1%) ukusabela okungalungile. I-Myocarditis iholele ekuyekisweni unomphela kwe-Opdualag ku-1.7% weziguli.

Okunye Ukusabela Okubi Okuvikelwe Kwamasosha Omzimba

Ama-IMAR alandelayo abalulekile emtholampilo enzeka ku-<1% (ngaphandle kwalapho kuphawulwe ngenye indlela) ezigulini ezithole i-Opdualag noma ezibikwe ngokusetshenziswa kwamanye amasosha omzimba avimbela i-PD-1/PD-L1. Kuye kwabikwa amacala anzima noma abulalayo ngenxa yalokhu kusabela okubi: Ci-ardiac/Vascular: i-vasculitis, i-pericarditis; Uhlelo Lwezinzwa: i-meningitis, i-encephalitis, i-myelitis ne-demyelination, i-myasthenic syndrome/i-myasthenia gravis (kuhlanganise nokukhushulwa), i-Guillain-Barré syndrome, i-nerve paresis, i-autoimmune neuropathy; I-Ocular: uveitis, iritis, nezinye izinto ezinobuthi ezivuthayo zamehlo zingenzeka. Ezinye izimo zingahlotshaniswa ne-retinal detachment. Amabanga ahlukahlukene okukhubazeka kokubona, okuhlanganisa ubumpumputhe, angenzeka. Uma i-uveitis yenzeka ihlangene namanye ama-IMAR, cabanga nge-Vogt-Koyanagi-Harada–like syndrome, njengoba lokhu kungase kudinge ukwelashwa nge-systemic steroids ukunciphisa ingozi yokulahlekelwa umbono unomphela; Amathumbu: pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis; Izicubu ze-Musculoskeletal kanye ne-Connective: i-myositis/i-polymyositis, i-rhabdomyolysis (kanye nemiphumela ehlobene kuhlanganise nokwehluleka kwezinso), isifo samathambo, i-polymyalgia rheumatica; I-Endocrine: i-hypoparathyroidism; Okunye (Hematologic/Immune): i-hemolytic anemia, i-aplastic anemia, i-hemophagocytic lymphohistiocytosis, i-systemic inflammatory response syndrome, i-hitiocytic necrotizing lymphadenitis (i-Kikuchi lymphadenitis), i-sarcoidosis, i-immune thrombocytopenic purpura, ukwenqatshwa kokufakelwa kwesitho esiqinile.

Ukusabela Okuhlobene Nokungeniswa

I-Opdualag ingabangela ukusabela okukhulu okuhlobene nokumnika. Yeka ukusebenzisa i-Opdualag ezigulini ezinokusabela okuhlobene nokumnika okunamandla noma okusongela ukuphila. Phakamisa noma yehlisa izinga lokumnika ezigulini ezinokusabela okuhlobene nokumnika okumaphakathi kuya kokumaphakathi. Ezigulini ezithole i-Opdualag njengokufakwa emthanjeni kwemizuzu engama-60, ukusabela okuhlobene nokumnika kwenzeka kuma-7% (23/355) eziguli.

Izinkinga ze-Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Izinkinga ezibulalayo nezinye ezinzima zingenzeka ezigulini ezithola i-allogeneic hematopoietic stem cell transplantation (HSCT) ngaphambi noma ngemva kokwelashwa nge-PD-1/PD-L1 receptor blocking antibody. Izinkinga ezihlobene nokufakelwa zihlanganisa isifo se-hyperacute graft-versus-host (GVHD), i-acute GVHD, i-GVHD engapheli, isifo se-hepatic veno-occlusive ngemva kokunciphisa isimo sokuqina, kanye nesifo se-steroid esidinga i-febrile syndrome (ngaphandle kwesizathu esithathelwanayo esihlonziwe). Lezi zinkinga zingase zenzeke naphezu kokungenelela kokwelashwa phakathi kwe-PD-1/PD-L1 blockade kanye ne-allogeneic HSCT.

Landela iziguli eduze ukuze uthole ubufakazi bezinkinga ezihlobene nokufakelwa futhi ungenelele ngokushesha. Cabangela inzuzo eqhathaniswa nezingozi zokwelashwa nge-PD-1/PD-L1 receptor blocking antibody ngaphambi noma ngemva kwe-allogeneic HSCT.

Ubuthi be-Embryo-Fetal

Ngokusekelwe endleleni yokwenza kwayo kanye nedatha evela ezifundweni zezilwane, i-Opdualag ingabangela ukulimala kwengane uma inikezwa owesifazane okhulelwe. Yeluleka abesifazane abakhulelwe ngengozi engaba khona ku-fetus. Yeluleka abesifazane abanamandla okuzala ukuthi basebenzise ukuvimbela inzalo okusebenzayo ngesikhathi sokwelashwa nge-Opdualag okungenani izinyanga ezingu-5 ngemva komthamo wokugcina we-Opdualag.

Isisu

Ayikho idatha mayelana nokuba khona kwe-Opdualag obisini lomuntu, imiphumela enganeni encela ibele, noma umphumela ekukhiqizweni kobisi. Ngenxa yokuthi i-nivolumab ne-relatlimab zingase zikhishwe obisini lomuntu futhi ngenxa yokuthi kungenzeka kube nemiphumela emibi enganeni enganeni, yeluleka iziguli ukuthi zingancelisi ibele ngesikhathi sokwelashwa nge-Opdualag futhi okungenani izinyanga ezi-5 ngemuva komthamo wokugcina.

Ukusabela Okubi Okubi

Ku-Relativity-047, ukusabela okubi okubulalayo kwenzeka ku-3 (0.8%) yeziguli ezalashwa nge-Opdualag; lezi zihlanganisa i-hemophagocytic lymphohistiocytosis, i-acute edema yamaphaphu, kanye ne-pneumonia. Ukusabela okubi kakhulu kwenzeka kuma-36% eziguli ezelashwe nge-Opdualag. Ukusabela okubi okuvame kakhulu okubikwe ku-≥1% weziguli ezelashwa nge-Opdualag kwaba ukungasebenzi kahle kwezindlala ze-adrenal (1.4%), i-anemia (1.4%), i-colitis (1.4%), inyumoniya (1.4%), i-acute myocardial infarction (1.1%), ubuhlungu beqolo (1.1%), isifo sohudo (1.1%), i-myocarditis (1.1%), kanye ne-pneumonitis (1.1%).

Ukusabela Okubi Okujwayelekile kanye Nokungajwayelekile Kwelabhorethri

Ukusabela okubi okuvame kakhulu okubikwe ku-≥20% weziguli ezelashwa nge-Opdualag kwakuwubuhlungu be-musculoskeletal (45%), ukukhathala (39%), ukuqubuka (28%), pruritus (25%), kanye nesifo sohudo (24%).

Ukukhubazeka okuvame kakhulu kwaselabhorethri okwenzeke ku-≥20% weziguli ezelashwe nge-Opdualag ukwehla kwe-hemoglobin (37%), ukwehla kwama-lymphocyte (32%), ukukhuphuka kwe-AST (30%), ukukhuphuka kwe-ALT (26%), nokuncipha kwe-sodium (24). %).

Please see U.S. Full Prescribing Information for Opdualag.

I-OPDIVO + YERVOY INDICATIONS

I-OPDIVO^® (i-nivolumab), njenge-ejenti eyodwa, ikhonjiswa ekwelapheni iziguli ezine-melanoma enganqandeki noma e-metastatic.

I-OPDIVO^® (nivolumab), ngokuhlangana ne-YERVOY^® (ipilimumab), ikhonjiswa ekwelapheni iziguli ezine-melanoma enganqandeki noma e-metastatic.

I-OPDIVO + YERVOY ULWAZI OLUBALULEKILE LOKUPHEPHA

Ukusabela Okubi Okunamandla Futhi Okubulalayo Komzimba

Ukuphendula okuphikisayo kokuvikela omzimba okubalwe lapha kungahle kungafaki konke ukusabela okubi kakhulu okungenzeka kube kubi futhi kuyabulala okuvikelwa ngumzimba.

Ukusabela okweqile kokulamula komzimba, okungaba nzima noma kubulale, kungenzeka kunoma yiluphi uhlelo lwesitho noma izicubu. Ngenkathi ukusabela okuphikisayo okuvikelwe ngumzimba kuvame ukuvela ngesikhathi sokwelashwa, kungenzeka futhi ngemuva kokuyekiswa kwe-OPDIVO noma i-YERVOY. Ukukhonjwa kwasekuqaleni nokuphathwa kubalulekile ukuqinisekisa ukusetshenziswa okuphephile kwe-OPDIVO ne-YERVOY. Ukuqapha izimpawu nezimpawu ezingaba ukubonakaliswa komtholampilo kokungqubuzana okuphikisayo okuvikelwe ngumzimba. Linganisa amakhemikhali asemtholampilo afaka ama-enzyme wesibindi, i-creatinine, i-adrenocorticotropic hormone (ACTH), nokusebenza kwegiloji ekuqaleni futhi ngezikhathi ezithile ngesikhathi sokwelapha i-OPDIVO nangaphambi komthamo ngamunye we-YERVOY. Ezimweni zokusola okungahambi kahle okusolwa ngokuzivikela komzimba, qala umsebenzi ofanele wokukhipha ezinye izindlela zokuziphatha, kufaka phakathi ukutheleleka. Faka ukuphathwa kwezokwelapha ngokushesha, kufaka phakathi ukubonisana okukhethekile njengoba kufanele.

Vimba noma unqamule unomphela i-OPDIVO ne-YERVOY ngokuya ngobukhulu (sicela ubheke isigaba 2 Isikali Nokuphathwa kulwazi oluhambisana nalokhu olugcweleyo). Ngokuvamile, uma ukuphazamiseka kwe-OPDIVO noma kwe-YERVOY kuyadingeka, phatha ukwelashwa kwe-systemic corticosteroid (1 kuye ku-2 mg / kg / ngosuku i-prednisone noma okulinganayo) kuze kube ngcono ku-Grade 1 noma ngaphansi. Lapho uthuthukela ku-Grade 1 noma ngaphansi, qalisa i-corticosteroid taper bese uqhubeka nokuthwebula okungenani inyanga eyodwa. Cabanga ngokuphathwa kwamanye ama-systemic immunosuppressants ezigulini ezinokuphendula okungathandeki okuvikelwe amasosha omzimba okungalawulwa ukwelashwa kwe-corticosteroid. Imihlahlandlela yokuphathwa kobuthi bokuphendula okungadingi ukuthi kudinge i-systemic steroids (isb., I-endocrinopathies kanye ne-dermatologic reaction) ixoxwa ngezansi.

I-Pneumonitis Yokuzivikela Emzimbeni

I-OPDIVO kanye ne-YERVOY kungabangela i-immune-mediated pneumonia. Izehlakalo ze-pneumonia ziphezulu ezigulini ezithole imisebe ye-thoracic ngaphambili. Ezigulini ezithola i-OPDIVO monotherapy, i-immune-mediated pneumonitis yenzeke ku-3.1% (61/1994) yeziguli, kuhlanganise neBanga lesi-4 (<0.1%), iBanga lesi-3 (0.9%), neBanga lesi-2 (2.1%).

Ezigulini ezithola i-OPDIVO 1 mg / kg ene-YERVOY 3 mg / kg njalo emavikini ama-3, i-pneumonitis elawulwa ngumzimba yenzeka ngo-7% (31/456) weziguli, kufaka phakathi iBanga 4 (0.2%), iBanga 3 (2.0%), kanye Ibanga 2 (4.4%).

I-Immune-Mediated Colitis

I-OPDIVO kanye ne-YERVOY kungabangela ukuqunjelwa kwe-immune-mediated, okungase kubulale. Uphawu oluvamile olufakwe encazelweni ye-colitis kwakuwuhudo. Ukutheleleka kwe-Cytomegalovirus (CMV) / ukuvuselelwa kuye kwabikwa ezigulini ezine-corticosteroid-refractory immune-mediated colitis. Ezimeni ze-corticosteroid-refractory colitis, cabanga ukuphindaphinda ukusebenza okuthelelanayo ukuze ukhiphe ezinye izimbangela. Ezigulini ezithola i-OPDIVO monotherapy, i-immune-mediated colitis yenzeke ku-2.9% (58/1994) yeziguli, kuhlanganise neBanga lesi-3 (1.7%) kanye neBanga lesi-2 (1%). Ezigulini ezithola i-OPDIVO 1 mg/kg nge-YERVOY 3 mg/kg njalo emavikini ama-3, i-immune-mediated colitis yenzeke kuma-25% (115/456) eziguli, okuhlanganisa iBanga lesi-4 (0.4%), iBanga lesi-3 (14%) kanye neBanga. 2 (8%).

Isifo Sokusha Kwesibindi Esiphakathi Nomzimba kanye neHepatotoxicity

I-OPDIVO ne-YERVOY ingabangela isifo sokusha kwesibindi sokuzivikela komzimba. Ezigulini ezithola i-OPDIVO monotherapy, isifo sokusha kwesibindi sokuzivikela komzimba senzeka ku-1.8% (35/1994) weziguli, okuhlanganisa iBanga lesi-4 (0.2%), iBanga lesi-3 (1.3%), neBanga lesi-2 (0.4%). Ezigulini ezithola i-OPDIVO 1 mg/kg nge-YERVOY 3 mg/kg njalo emavikini ama-3, ukusha kwesibindi kokuzivikela komzimba kwenzeka ku-15% (70/456) weziguli, okuhlanganisa iBanga lesi-4 (2.4%), iBanga lesi-3 (11%), kanye Ibanga lesi-2 (1.8%).

Ama-Endocrinopathies Azivikela Omzimba

I-OPDIVO ne-YERVOY kungadala ukungasebenzi kahle kwe-adrenal eyinhloko noma yesibili, i-hypophysitis evikelekile ekulweni komzimba, ukuphazamiseka kwe-thyroid okulamula amasosha omzimba, kanye nohlobo 1 lwesifo sikashukela, esingabonisa nge-ketoacidosis yesifo sikashukela. Bamba i-OPDIVO ne-YERVOY ngokuya ngobukhulu (sicela ubheke isigaba 2 Isikali Nokuphatha kulwazi oluhambisana nalokhu oluphelele). Ekufundeni kweBanga 2 noma ngaphezulu kwe-adrenal, qalisa ukwelashwa okuyizimpawu, kufaka phakathi ukushintshwa kwehomoni njengoba kukhonjisiwe emtholampilo. I-Hypophysitis ingaletha ngezimpawu ezibukhali ezihambisana nomphumela wobuningi obufana nekhanda, i-photophobia, noma ukukhubazeka kwenkambu ebonakalayo. I-Hypophysitis ingadala i-hypopituitarism; qala ukufaka ama-hormone njengoba kukhonjisiwe emtholampilo. I-Thyroiditis ingabonisa nge-endocrinopathy noma ngaphandle kwayo. I-Hypothyroidism ingalandela i-hyperthyroidism; qala ukufaka esikhundleni se-hormone noma ukuphathwa kwezokwelapha njengoba kukhonjisiwe emtholampilo. Gada iziguli ze-hyperglycemia noma ezinye izimpawu nezimpawu zesifo sikashukela; qala ukwelashwa nge-insulin njengoba kukhonjisiwe emtholampilo.

Ezigulini ezithola i-OPDIVO monotherapy, ukungasebenzi kahle kwezindlala ze-adrenal kwenzeka ku-1% (20/1994), okuhlanganisa iBanga lesi-3 (0.4%) neBanga lesi-2 (0.6%).Ezigulini ezithola i-OPDIVO 1 mg/kg ene-YERVOY 3 mg/kg njalo emavikini ama-3. , ukungasebenzi kahle kwezindlala ze-adrenal kwenzeka ku-8% (35/456), kuhlanganise neBanga lesi-4 (0.2%), iBanga lesi-3 (2.4%), neBanga lesi-2 (4.2%). Ezigulini ezithola i-OPDIVO 1 mg/kg nge-YERVOY 3 mg/kg njalo emavikini ama-3, ukungasebenzi kahle kwe-adrenal kwenzeka ku-8% (35/456), okuhlanganisa iBanga lesi-4 (0.2%), iBanga 3 (2.4%), neBanga lesi-2 (4.2) %).

Ezigulini ezithola i-OPDIVO monotherapy, i-hypophysitis yenzeke ku-0.6% (12/1994) yeziguli, kuhlanganise neBanga lesi-3 (0.2%) kanye neBanga lesi-2 (0.3%). Ezigulini ezithola i-OPDIVO 1 mg/kg nge-YERVOY 3 mg/kg njalo emavikini angu-3, ​​i-hypophysitis yenzeke ku-9% (42/456), kuhlanganise neBanga lesi-3 (2.4%) kanye neBanga lesi-2 (6%).

Ezigulini ezithola i-OPDIVO monotherapy, i-thyroiditis yenzeke ku-0.6% (12/1994) weziguli, kufaka phakathi iBanga 2 (0.2%).

Ezigulini ezithola i-OPDIVO monotherapy, i-hyperthyroidism yenzeke ku-2.7% (54/1994) yeziguli, kuhlanganise neBanga lesi-3 (<0.1%) kanye neBanga lesi-2 (1.2%). Ezigulini ezithola i-OPDIVO 1 mg/kg nge-YERVOY 3 mg/kg njalo emavikini ama-3, i-hyperthyroidism yenzeke ku-9% (42/456) weziguli, okuhlanganisa iBanga lesi-3 (0.9%) neBanga lesi-2 (4.2%).

Ezigulini ezithola i-OPDIVO monotherapy, i-hypothyroidism yenzeke ku-8% (163/1994) yeziguli, kuhlanganise neBanga lesi-3 (0.2%) kanye neBanga lesi-2 (4.8%). Ezigulini ezithola i-OPDIVO 1 mg/kg nge-YERVOY 3 mg/kg njalo emavikini ama-3, i-hypothyroidism yenzeke ku-20% (91/456) weziguli, okuhlanganisa iBanga lesi-3 (0.4%) neBanga lesi-2 (11%).

Ezigulini ezithola i-OPDIVO monotherapy, isifo sikashukela senzeke ku-0.9% (17/1994) weziguli, kufaka phakathi iBanga 3 (0.4%) neBanga 2 (0.3%), namacala ama-2 wesifo sikashukela ketoacidosis.

I-Nephritis Yokuzivikela Emzimbeni enokungasebenzi kahle kwe-Renal

I-OPDIVO kanye ne-YERVOY kungabangela i-nephritis ye-immune-mediated. Ezigulini ezithola i-OPDIVO monotherapy, i-immune-mediated nephritis kanye nokungasebenzi kahle kwezinso kwenzeka ku-1.2% (23/1994) yeziguli, okuhlanganisa iBanga lesi-4 (<0.1%), iBanga lesi-3 (0.5%), neBanga lesi-2 (0.6%).

Ukusabela Okungahambi kahle Kwe-Dermatologic

I-OPDIVO ingadala ukuqhuma kwamasosha omzimba noma i-dermatitis. I-Exfoliative dermatitis, kufaka phakathi i-Stevens-Johnson syndrome (SJS), i-epidermal necrolysis enobuthi (TEN), kanye nokuqubuka kwezidakamizwa nge-eosinophilia kanye nezimpawu zesistimu (i-DRESS) kwenzeke ngama-antibody okuvimba i-PD-1 / PD-L1. Ama-topical emollients kanye / noma ama-corticosteroids ama-topical angahle anele ukwelapha ukuqubuka okungekho emthethweni noma okumaphakathi.

I-YERVOY ingabangela ukuqubuka kwe-immune mediated noma i-dermatitis, okuhlanganisa i-bullous and exfoliative dermatitis, i-SJS, i-TEN, ne-DRESS. Ama-topical emollients kanye/noma ama-topical corticosteroids angase anele ukwelapha ukuqubuka okungeyona i-bullous/exfoliative okumaphakathi kuya kokumaphakathi.

Vimba noma unqamule unomphela i-OPDIVO ne-YERVOY ngokuya ngobukhulu (sicela ubheke isigaba 2 Isikali Nokuphathwa kulwazi oluhambisana nalokhu olugcweleyo).

Ezigulini ezithola i-OPDIVO monotherapy, ukuqubuka kwe-immune-mediated kwenzeka ku-9% (171/1994) yeziguli, kuhlanganise neBanga lesi-3 (1.1%) kanye neBanga lesi-2 (2.2%). Ezigulini ezithola i-OPDIVO 1 mg/kg nge-YERVOY 3 mg/kg njalo emavikini angu-3, ​​ukuqubuka kwe-immune mediated kwenzeka kuma-28% (127/456) eziguli, okuhlanganisa iBanga lesi-3 (4.8%) kanye neBanga lesi-2 (10%).

Okunye Ukusabela Okubi Okuvikelwe Kwamasosha Omzimba

Ukusabela okulandelayo okubalulekile okubalulekile emtholampilo kwe-immune-mediated kwenzeke ku-<1% (ngaphandle kwalapho kuphawulwe ngenye indlela) ezigulini ezithole i-OPDIVO monotherapy noma i-OPDIVO ngokuhlanganiswa ne-YERVOY noma ezibikwe ngokusetshenziswa kokunye ukuvinjwa kwe-PD-1/PD-L1 amasosha omzimba. Kuye kwabikwa amacala anzima noma abulalayo ngenxa yalokhu kusabela okubi: inhliziyo/mithambo: i-myocarditis, i-pericarditis, i-vasculitis; uhlelo lwezinzwa: i-meningitis, i-encephalitis, i-myelitis ne-demyelination, i-myasthenic syndrome/i-myasthenia gravis (kuhlanganise nokuqina), i-Guillain-Barré syndrome, i-nerve paresis, i-autoimmune neuropathy; amehlo: uveitis, iritis, nezinye izinto ezinobuthi ezivuthayo zamehlo zingenzeka; Amathumbu: i-pancreatitis ukufaka ukwanda kwe-serum amylase kanye namazinga e-lipase, i-gastritis, i-duodenitis; izicubu ze-musculoskeletal kanye nezixhumi: i-myositis/i-polymyositis, i-rhabdomyolysis, kanye nemiphumela ehambisanayo ehlanganisa ukuhluleka kwezinso, isifo samathambo, i-polymyalgia rheumatica; uhlelo lwe-endocrine: i-hypoparathyroidism; okunye (i-hematological/immune): i-hemolytic anemia, i-aplastic anemia, i-hemophagocytic lymphohistiocytosis (HLH), i-systemic inflammatory response syndrome, i-histiocytic necrotizing lymphadenitis (i-Kikuchi lymphadenitis), i-sarcoidosis, i-immune thrombocytopenic purpura, ukwenqatshwa kokufakelwa kwesitho esiqinile.

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: uhlelo lwezinzwa: i-autoimmune neuropathy (2%), i-myasthenic syndrome/myasthenia gravis, ukungasebenzi kahle kwezimoto; inhliziyo nemithambo yegazi: i-angiopathy, i-arteritis yesikhashana; amehlo: i-blepharitis, i-episcleritis, i-orbital myositis, i-scleritis; Amathumbu: i-pancreatitis (1.3%); okunye (i-hematological/immune): i-conjunctivitis, i-cytopenia (2.5%), i-eosinophilia (2.1%), i-erythema multiforme, i-hypersensitivity vasculitis, i-neurosensory hypoacusis, i-psoriasis.

Amanye amacala we-IMAR we-ocular angahlotshaniswa neqembu le-retinal. Amamaki ahlukahlukene wokukhubazeka okubonakalayo, kufaka phakathi ukungaboni, angenzeka. Uma i-uveitis ivela ngokuhlangana nokunye ukusabela okuphikisayo okuvikelwa amasosha omzimba, cabanga nge-Vogt-Koyanagi-Harada-like syndrome, ebonwe ezigulini ezithola i-OPDIVO ne-YERVOY, njengoba lokhu kungadinga ukwelashwa ngama-systemic corticosteroids ukunciphisa ubungozi bokubona unomphela ukulahlekelwa.

Ukusabela Okuhlobene Nokungeniswa

I-OPDIVO kanye ne-YERVOY kungabangela ukusabela okubi okuhlobene nokumnika. Yeka ukusebenzisa i-OPDIVO ne-YERVOY ezigulini ezinokusabela okuhlobene nokumnika okuhlobene kakhulu (iBanga lesi-3) noma okusongela ukuphila (iBanga lesi-4). Ukuphazamisa noma ukunciphisa izinga lokumnika ezigulini ezinokusabela okuhlobene nokumnika okuncane (iBanga loku-1) noma okumaphakathi (Ibanga lesi-2).

Ezigulini ezithola i-OPDIVO monotherapy njengokufakwa kwemizuzu engama-60, ukusabela okuhlobene nokumnika kwenzeka ku-6.4% (127/1994) weziguli. Ocwaningweni oluhlukile lapho iziguli zithole i-OPDIVO monotherapy njengokufakwa kwemizuzu engama-60 noma ukumnika imizuzu engama-30, ukusabela okuhlobene nokumnika kwenzeka ku-2.2% (8/368) no-2.7% (10/369) weziguli, ngokulandelana. Ukwengeza, u-0.5% (2/368) kanye no-1.4% (5/369) weziguli, ngokulandelana, waba nokusabela okungekuhle phakathi namahora angu-48 wokumnika okuholele ekubambezelekeni komthamo, ukuyeka unomphela noma ukubanjwa kwe-OPDIVO.

Ezigulini ze-melanoma ezithola i-OPDIVO 1 mg / kg nge-YERVOY 3 mg / kg njalo emavikini ama-3, ukusabela okuhlobene nokumnika kwenzeka ku-2.5% (10/407) yeziguli.

Izinkinga ze-Allogeneic Hematopoietic Stem Cell Transplantation

Izinkinga ezibulalayo nezinye ezinzima zingenzeka ezigulini ezithola ukufakelwa i-allogeneic hematopoietic stem cell transplantation (HSCT) ngaphambi noma ngemuva kokuphathwa nge-OPDIVO noma i-YERVOY. Izinkinga ezihlobene nokufakelwa zifaka phakathi i-hyperacute graft-versus-host-disease (i-GVHD), i-GVHD ebukhali, i-GVHD engapheli, isifo se-hepatic veno-occlusive (VOD) ngemuva kokuncipha kwesimo sokuqina, kanye ne-steroid-edinga i-febrile syndrome (ngaphandle kwesizathu esithathelwanayo esikhonjisiwe). Lezi zinkinga zingenzeka naphezu kokwelapha okungenelela phakathi kwe-OPDIVO noma i-YERVOY ne-allogeneic HSCT.

Landela iziguli eduze ukuze uthole ubufakazi bezinkinga ezihlobene nokufakelwa bese ungenelela ngokushesha. Cabanga ngenzuzo uma uqhathanisa nobungozi bokwelashwa nge-OPDIVO ne-YERVOY ngaphambi noma ngemuva kwe-HSCT ye-allogeneic.

Ubuthi be-Embryo-Fetal

Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.

Ukufa okwandayo ezigulini ezine-Multiple Myeloma lapho i-OPDIVO ingezwa ku-Thalidomide Analogue naseDexamethasone

Ezivivinyweni zomtholampilo ezingahleliwe ezigulini ezine-myeloma eningi, ukwengezwa kwe-OPDIVO kwi-analogue ye-thalidomide kanye ne-dexamethasone kuholele ekwandeni kokufa kwabantu. Ukwelashwa kweziguli ezine-myeloma eminingi ene-PD-1 noma i-PD-L1 evimba i-antibody ngokuhlanganiswa ne-analogue ye-thalidomide kanye ne-dexamethasone akunconywa ngaphandle kwezilingo zomtholampilo ezilawulwayo.

Isisu

Ayikho idatha ebukhoneni be-OPDIVO noma i-YERVOY obisini lomuntu, imiphumela enganeni eyanceliswa, noma imiphumela ekukhiqizeni ubisi. Ngenxa yamandla okuphendula okungathi sína ezinganeni ezincelisayo, yala abesifazane ukuthi bangancelisi ngesikhathi sokwelashwa nangezinyanga ezi-5 ngemuva komthamo wokugcina.

Ukusabela Okubi Okubi

Ku-Checkmate 037, ukusabela okubi kakhulu kwenzeke kuma-41% eziguli ezithola i-OPDIVO (n=268). Ukusabela okungekuhle kweBanga lesi-3 nelesi-4 kwenzeka ku-42% weziguli ezithola i-OPDIVO. Ukusabela okubi kakhulu kweBanga lesi-3 nelesi-4 kwezidakamizwa okubikwe ku-2% kuya ku-5% yeziguli ezithola i-OPDIVO kwakuwubuhlungu besisu, i-hyponatremia, ukwanda kwe-aspartate aminotransferase, kanye ne-lipase eyandayo. Ku-Checkmate 066, ukusabela okubi kakhulu kwenzeke kuma-36% eziguli ezithola i-OPDIVO (n=206). Ukusabela okungekuhle kweBanga lesi-3 nelesi-4 kwenzeka ku-41% weziguli ezithola i-OPDIVO. Ukusabela okubi kakhulu kweBanga lesi-3 nelesi-4 okubikwe ku-≥2% weziguli ezithola i-OPDIVO kwaba ukwanda kwe-gamma-glutamyltransferase (3.9%) kanye nesifo sohudo (3.4%). Ku-Checkmate 067, ukusabela okubi kakhulu (74% no-44%), ukusabela okubi okuholela ekuyekisweni unomphela (47% no-18%) noma ekubambezelekeni komthamo (58% no-36%), kanye neBanga lesi-3 noma lesi-4 ukusabela okungekuhle (72% kanye nama-51%) konke kwenzeke kaningi engalweni ye-OPDIVO kanye ne-YERVOY (n=313) ngokuhlobene nengalo ye-OPDIVO (n=313). Okuvame kakhulu (≥10%) ukusabela okubi kakhulu engalweni ye-OPDIVO plus YERVOY kanye nengalo ye-OPDIVO, ngokulandelana, kwaba isifo sohudo (13% no-2.2%), i-colitis (10% no-1.9%), ne-pyrexia (10% kanye no-1.0) %).

Ukusabela Okuvamile Okubi

Ku-Checkmate 037, ukusabela okungavamile okuvame kakhulu (≥20%) okubikwe nge-OPDIVO (n=268) kwaba ukuqubuka (21%). Ku-Checkmate 066, ukusabela okubi okuvame kakhulu (≥20%) okubikwe nge-OPDIVO (n=206) vs dacarbazine (n=205) kwaba ukukhathala (49% vs 39%), ubuhlungu be-musculoskeletal (32% vs 25%), ukuqubuka (28% vs 12%), kanye ne-pruritus (23% vs 12%). Ku-Checkmate 067, ukusabela okungavamile (≥20%) okuvame kakhulu ku-OPDIVO plus YERVOY ingalo (n=313) kwaba ukukhathala (62%), isifo sohudo (54%), ukuqubuka (53%), isicanucanu (44%), i-pyrexia (40%), pruritus (39%), ubuhlungu be-musculoskeletal (32%), ukuhlanza (31%), ukuncipha kwesifiso sokudla (29%), ukukhwehlela (27%), ikhanda elibuhlungu (26%), ukuphefumula (24%), ukutheleleka komgudu wokuphefumula ophezulu (23%), i-arthralgia (21%), kanye nama-transaminase ayanda (25%). Ku-Checkmate 067, okuvame kakhulu (≥20%) ukusabela okubi engalweni ye-OPDIVO (n=313) kwaba ukukhathala (59%), ukuqubuka (40%), ubuhlungu be-musculoskeletal (42%), isifo sohudo (36%), isicanucanu. (30%), ukukhwehlela (28%), pruritus (27%), ukutheleleka komgudu wokuphefumula ophezulu (22%), ukuncipha kokudla (22%), ikhanda elibuhlungu (22%), ukuqunjelwa (21%), arthralgia (21%). , kanye nokuhlanza (20%).

Please see US Full Prescribing Information for OPDIVO and YERVOY.

IBristol Myers Squibb: Ukwakha Ikusasa Elihle Labantu Abanomdlavuza

IBristol Myers Squibb iphefumulelwe ngumbono owodwa - ukuguqula izimpilo zeziguli ngesayensi. Inhloso yocwaningo lomdlavuza wenkampani ukuletha imishanguzo enikeza isiguli ngasinye impilo engcono, enempilo nokwenza ukwelashwa kube nokwenzeka. Ukwakha ifa ebangeni elibanzi lomdlavuza okushintshe okulindelwe ukusinda kwabaningi, abacwaningi beBristol Myers Squibb bahlola imingcele emisha yokwelapha okwenzelwe wena, nangamapulatifomu amasha wedijithali, baphendulela idatha ekuqondeni okucija ukugxila kwabo. Ubungcweti besayensi obujulile, amakhono okusika kanye nezinkundla zokutholwa kwenza inkampani ibheke umdlavuza kuzo zonke izinhlangothi. Umdlavuza ungaba nengqondo engapheli ezingxenyeni eziningi zempilo yesiguli, kanti uBristol Myers Squibb uzibophezele ekuthatheni izinyathelo ukubhekana nazo zonke izici zokunakekelwa, kusukela ekuhlonzweni kuya ekusindeni. Ngoba njengomholi ekunakekelweni komdlavuza, uBristol Myers Squibb usebenza ukunika amandla bonke abantu abanomdlavuza ukuze babe nekusasa elingcono.

Mayelana Nokwesekwa Kokufinyelela Kwesiguli kweBristol Myers Squibb

I-Bristol Myers Squibb isalokhu izibophezele ekunikezeni usizo ukuze iziguli ezinomdlavuza ezidinga imithi yethu zikwazi ukuyifinyelela futhi zisheshise isikhathi sokwelashwa.

I-BMS Access Support^®, the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support can be obtained by calling BMS Access Supportat 1-800-861-0048 or by visiting www.bmsaccesssupport.com.

Mayelana neBristol Myers Squibb kanye ne-Ono Pharmaceutical Collaboration

Ngo-2011, ngesivumelwano sokusebenzisana ne-Ono Pharmaceutical Co., iBristol Myers Squibb yandisa amalungelo ayo endawo ukuze ithuthuke futhi ihwebe. I-Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

Mayelana neBristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.

I-Celgene neJuno Therapeutics ziyizinkampani ezingaphansi eziphethwe ngokuphelele I-Bristol-Myers Squibb Inkampani. Emazweni athile angaphandle kwase-US, ngenxa yemithetho yendawo, i-Celgene neJuno Therapeutics kubhekiselwa kuyo ngokuthi, i-Celgene, inkampani ye-Bristol Myers Squibb kanye ne-Juno Therapeutics, inkampani ye-Bristol Myers Squibb.

Isitatimende Esiyisixwayiso Ngokuphathelene Nezitatimende Zokubheka Phambili

Lokhu kukhululwa kwabezindaba kuqukethe "izitatimende ezibheke phambili" ngaphakathi kwencazelo ye-Private Securities Litigation Reform Act ka-1995 mayelana, phakathi kwezinye izinto, ucwaningo, ukuthuthukiswa nokudayiswa kwemikhiqizo yezemithi. Zonke izitatimende ezingezona izitatimende zamaqiniso omlando ziyizitatimende, noma zingathathwa njengezibheke phambili. Izitatimende ezinjalo ezibheke phambili zisekelwe kulokho okulindelwe manje kanye nokuqagela mayelana nemiphumela yethu yezezimali yesikhathi esizayo, imigomo, izinhlelo nezinjongo futhi kuhilela ubungozi obungokwemvelo, ukuqagela nokungaqiniseki, okuhlanganisa izici zangaphakathi noma zangaphandle ezingase zibambezeleke, ziphambukise noma ziguqule noma iyiphi yazo kokulandelayo. iminyaka embalwa, okunzima ukuyibikezela, ingaba ngaphezu kwamandla ethu futhi ingabangela imiphumela yethu yezezimali yesikhathi esizayo, imigomo, izinhlelo kanye nezinjongo zehluke kakhulu kulezo ezivezwe, noma ezishiwo, izitatimende. Lezi zingozi, ukuqagela, ukungaqiniseki nezinye izici zihlanganisa, phakathi kokunye, noma ngabe i-Opdualag^TM (i-nivolumab kanye ne-relatlimab-rmbw) izophumelela ngokwezentengiselwano ngenkomba echazwe kulokhu kukhululwa kwabezindaba, noma yikuphi ukugunyazwa kokumaketha, uma kuvunyiwe, kungase kube nemikhawulo ebalulekile ekusetshenzisweni kwayo, kanye nalokho kuvunyelwa okuqhubekayo kwalowo mkhiqizo okhethiwe walolu hlobo lwenkomba echazwe kulo mbhalo. ukukhululwa kungase kuncike ekuqinisekisweni nasekuchazweni kwezinzuzo zomtholampilo ezivivinyweni eziqinisekisayo. Asikho isitatimende esibheke phambili esingaqinisekiswa. Izitatimende ezibheke phambili kulokhu kukhululwa kwabezindaba kufanele zihlaziywe kanye nezingozi eziningi nokungaqiniseki okuthinta ibhizinisi nemakethe ye-Bristol Myers Squibb, ikakhulukazi lezo ezishiwo esitatimendeni sokuxwayisa kanye nengxoxo yezinto eziyingozi kumbiko Wonyaka we-Bristol Myers Squibb Wefomu 10-K unyaka ophele mhla zingama-31 kuZibandlela, 2021, njengoba kubuyekezwe Imibiko yethu Yekota Elandelayo Yefomu 10-Q, Imibiko Yamanje Yefomu 8-K nokunye okugcwaliswe ngeKhomishini Yezibambiso Nokushintshaniswa. Izitatimende ezibheke phambili ezifakwe kulo mbhalo zenziwa kuphela kusukela ngosuku lwalo mbhalo futhi ngaphandle kwalapho kudingwa ngenye indlela umthetho osebenzayo, uBristol Myers Squibb akenzi isibopho sokubuyekeza esidlangalaleni noma ukubuyekeza noma yisiphi isitatimende esibheke phambili, noma ngabe kungenxa yalokhu. ulwazi olusha, izehlakalo zesikhathi esizayo, izimo ezishintshile noma okunye.

Okubhekwayo

1. I-Opdualag Ukubeka Ulwazi. I-Opdualag Ulwazi Lomkhiqizo wase-US. Kugcine ukubuyekezwa: Mashi 2022. Princeton, NJ: Bristol-Myers Squibb Company.
2. Tawbi HA, Schadendorf D, Lipson EJ, et al. I-Relatlimab ne-nivolumab ngokumelene ne-nivolumab ku-melanoma ethuthukisiwe engalashwanga. N Engl J Med. 2022; 386: 24-34.
3. Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. I-Nivolumab kanye ne-ipilimumab noma i-nivolumab iyodwa iqhathaniswa ne-ipilimumab iyodwa ku-melanoma ethuthukisiwe (CheckMate 067): Imiphumela yeminyaka emi-4 yohlolo lwe-multicentre, randomized, phase 3. I-Lancet Oncol. 2018;19(11): 1480-1492.
4. I-US Food & Drug Administration. Uhlelo Lokuhlola I-Oncology Yesikhathi Sangempela.